The transient nature of the Th17 phenotype.

CD4(+) Th lymphocytes represent a heterogeneous population of cells that play an essential role in adaptive immunity. In addition to type 1 (Th1) and type 2 (Th2) cells, a third subset of CD4(+) Th effector cells has recently been discovered, named type 17 (Th17) because of its unique ability to produce interleukin (IL)-17. Initial studies in mice suggested that Th17 cells are the pathogenic cells in autoimmune disorders, whereas Th1 cells are protective. Studies in humans have demonstrated the plasticity of Th17 cells and their ability to convert to Th1 cells. This Th17 to Th1 cell plasticity has also been confirmed in mice and, furthermore, it was found that Th17 cells appear to be pathogenic only when they shift to Th1 cells. A study in this issue of the European Journal of Immunology uses an IL-17 fate mapping mouse strain, which permits the identification of the cells that have been IL-17 producers, to provide definitive evidence that Th17 cells, either generated in vitro or in vivo, represent a transient phenotype that tend to convert into IFN-γ-producing cells. Our Commentary discusses this interesting point in light of previous data suggesting the same concept.